The Secretary of Agriculture forwarded the report to the American Association of State Highway Officials (AASHO), which represented the State highway agencies that owned and operated the roads proposed for the new system. Over the next months, State highway agencies contacted AASHO and the U.S. Bureau of Public Roads regarding desired changes.

Based on these changes, U.S. 52 had been altered by the time AASHO adopted the U.S. highway system by State ballot on November 11, 1926. The first official log of the approved system described U.S. 52 as:

United States Highway No. 53
Total Mileage, 343

West Virginia Beginning at Huntington on the West Virginia-Ohio State line.Ohio Beginning at Chesapeake, opposite Huntington, West Virginia, via Ironton, Portsmouth, Manchester, Ripley, New Richmond, Cincinnati to the Ohio-Indiana State line at Harrison.Indiana Beginning at the Ohio-Indiana State line at Harrison via Brookville, Rushville, Indianapolis, Lebanon, LaFayette to an intersection with United States Highway 41 northwest of Fowler.

The eastern portion of the original route had been shifted to U.S. 60 following one of the most contentious battles of the numbering phase. Kentucky had objected to the fact that the Joint Board had assigned U.S. 60, which should have begun on the East Coast and traveled through the State, to a route from Chicago, Illinois, to Los Angeles, California. After numerous proposals were considered for resolving the dispute among the States, a compromise was worked out. The original U.S. 60 became U.S. 66, while the number 60 was shifted onto a highway from Newport News to an intersection with U.S. 66 at Springfield, Missouri, incorporating some of the original mileage of U.S. 52.

On June 8, 1931, AASHO approved a shift in the eastern terminus of U.S. 52 to Bluefield via Lavalette and Williamson. This change was reflected in the next log of the U.S highway system, which indicated that U.S. 52 was now 547 miles long.

By the 1935 log, AASHO had approved an extension of U.S. 52 on both ends of the route. The log now read: